4-Nitrophenol → Acridin-1(2H)-one

Dissolve 1-O-DMT-2-(N-acridine-4-aminobutyryl)-1,3-propanediol (7.2 g, 10.4 mmol) (7) in 30 ml anhydrous pyridine with stirring. Stir at room temperature. Add p-dimethylamino-pyridine (0.584 g, 4.8 mmol) and succinic anhydride (0.863 g, 8.63 mmol). Stir reaction mixture at room temperature for 24 hours. Analyze by TLC to check whether reaction is completed, using 1:1 MeOH:CH2Cl2 with 4 drops of NH4OH added to develop; visualize with H2SO4 (Rf product=0.5). Remove solvent by rotary evaporation using high vacuum. Partition between 250 ml EtOAc and 100 ml H2O. Wash 3×130 ml brine. Combine aqueous layers and extract with 300 ml EtOAc. Dry the organics over anhydrous Na2SO4. Remove solvent by rotary evaporation in vacuo. Co-evaporate 2×50 ml anhydrous pyridine. Immediately add 41 ml anhydrous dioxane. Swirl flask to achieve complete solution. Add 7.5 ml anhydrous pyridine and p-nitrophenol (2.15 g, 15.5 mmol) to flask with magnetic stirring. Cool reaction flask to 25° C. Add dicyclohexylcarbodiimide (2.92 g, 14.3 mmol, MW 204.35) with stirring, and stir at room temperature for 4 hours. Add 1.6 ml triethylamine and stir 10 minutes. Filter reaction mixture through a sintered glass funnel directly into 18 g long chain alkylamine CPG. Agitate the CPG mixture for 24 hours. Collect the derivatized CPG by filtration into a clean 600 ml sintered glass funnel. Wash with 3×500 ml DMF, 3×500 ml MeOH, and 3×500 ml ether. Transfer the CPG to a clean, dry 500 ml RB flask and dry on the rotovap, using aspirator, then pump at hard vacuum for an hour to remove all solvents. Mix together 12.7 ml acetic anhydride, 51 ml anhydrous pyridine, and 236 mg DMAP. Cap the CPG by adding this solution to the dry CPG and swirl on orbital shaker for 2 hours. Collect the capped CPG by filtration in a clean 500 ml sintered glass funnel. Wash with 1×1000 ml pyridine, 3×500 ml DMF, 2×500 ml water, 3×500 ml MeOH, and 3×500 ml ether. Dry in vacuo. Yield: 18 g.

1. stirringStir at room temperature
2. stirringStir
3. customreaction mixture at room temperature for 24 hours
4. customAnalyze by TLC to check whether reaction
5. customRemove solvent by rotary evaporation
6. customPartition between 250 ml EtOAc and 100 ml H2O
7. washWash 3×130 ml brine
8. extractionCombine aqueous layers and extract with 300 ml EtOAc
9. dry with materialDry the organics over anhydrous Na2SO4
10. customRemove solvent by rotary evaporation in vacuo
11. customCo-evaporate 2×50 ml anhydrous pyridine
12. temperatureCool
13. customreaction flask to 25° C
14. stirringstir at room temperature for 4 hours
15. stirringstir 10 minutes
16. filtrationFilter
17. customreaction mixture through a sintered glass funnel directly into 18 g long chain alkylamine CPG
18. stirringAgitate the CPG mixture for 24 hours
19. customCollect the derivatized CPG
20. filtrationby filtration into a clean 600 ml sintered glass funnel
21. washWash with 3×500 ml DMF, 3×500 ml MeOH, and 3×500 ml ether
22. customdry 500 ml RB flask
23. customdry on the rotovap
24. waitpump at hard vacuum for an hour
25. customto remove all solvents
26. additionMix together 12.7 ml acetic anhydride, 51 ml anhydrous pyridine, and 236 mg DMAP
27. customCap the CPG
28. additionby adding this solution to the dry CPG
29. customCollect the capped CPG
30. filtrationby filtration in a clean 500 ml sintered glass funnel
31. washWash with 1×1000 ml pyridine, 3×500 ml DMF, 2×500 ml water, 3×500 ml MeOH, and 3×500 ml ether
32. customDry in vacuo

ORD record

ord-c8ae168ad4914c249e90cb455767482b

Source dataset

uspto-grants-1995_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05451463